The study of circadian rhythms in mammals allows us to address a broad spectrum of important questions in neuroscience involving cellular communication and the role of neuropeptides. We will focus on two important questions; 1) how VIP regulates intercellular communication and membrane excitability, and 2) how an attenuation or lack of the VIP signal affects circadian rhythms in physiology. The first question will be addressed by examining the effects of the VIP on gamma-aminobutyric acid (GABA)-evoked and intrinsic voltage-sensitive K+ currents in SCN neurons. The second question will be addressed by investigating animals that are deficient in VIP and determining how this disruption affects neuronal physiology. Mounting evidence from a variety of systems indicates that neuropeptides are present at many synaptic connections throughout the central nervous system (CNS), though their function is not completely understood. Understanding the mechanisms underlying VIP's effect on cellular excitability and communication in the SCN will provide us with a physiological explanation for many of the properties of not only circadian systems, but neuronal networks throughout the CNS. The whole-cell voltage-clamp recording techniques will be used to measure spontaneous synaptic currents and intrinsic membrane currents in SCN neurons visualized by infrared differential interference contrast (IR-DIC) videomicroscopy in a brain slice preparation of the C57bl mouse. Single-cell reverse transcription-PCR (RT-PCR) and immunocytochemistry will be used to identify the neuronal subtype.